We previously demonstrated that gadolinium endohedral metallofullerenol ([Gd@C82(OH)22]n nanoparticles) had high inhibitory activity on growth of malignant tumor in vivo by uncertain mechanism(s). The activities of enzymes associated with the metabolism of reactive oxygen species (ROS) were decreased in the tumor-bearing mice by intraperitoneally injection of [Gd@C82(OH)22]n nanoparticles . In current study, systemic investigation of the potential function of [Gd@C82(OH)22]n nanoparticles found that it expressed direct scavenging activity toward active species including DPPH, superoxide radical (O), hydroxyl radical (OH), nitric oxide (NO), singlet oxygen and strongly inhibited lipid peroxidation. Electron spin resonance (ESR) spectroscopy, the state-of-art technique to measure chemical species that have one or more unpaired electrons in parallel, was employed to measure active species scavenging activities of [Gd@C82(OH)22]n nanoparticles in vitro. Pre-treatment with [Gd@C82(OH)22]n nanoparticles significantly reduced ESR signal of DPPH, and expressed drastically scavenging activity toward superoxide (O) in xanthine/xanthine oxidase system. It decreased formation of hydroxyl radical (OH) with similar efficiency as nitric oxide (NO), and effectively hampered lipid peroxidation in vitro. In addition, [Gd@C82(OH)22]n nanoparticles demonstrated extensively scavenging activities of active species measured in vivo, which was consistent with reduced progression of cancer cells treated with [Gd@C82(OH)22]n nanoparticles. In summary, results obtained in this study revealed strong active species-scavenging activities of [Gd@C82(OH)22]n nanoparticles in vitro and in vivo. Scavenging activities of hydroxylated [Gd@C82(OH)22]n nanoparticles was systemically measured in different milieu, and demonstrated the inhibition of tumor progression by [Gd@C82(OH)22]n nanoparticles treatment likely due to removed active species.